The Canadian Cardiovascular Society (CCS) has developed a four-stage classification of acute atherothrombotic myocardial infarction (MI) based on the severity of the injury to the myocardium.
Relying on more than 50 years of data on acute MI with reperfusion therapy, the society has identified the following four stages of progressively worsening myocardial tissue injury:
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Aborted MI (no or minimal myocardial necrosis).
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MI with significant cardiomyocyte necrosis but without microvascular injury.
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Cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (that is, “no-reflow”).
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Cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage.
The classification is described in an expert consensus statement that was published October 28 in the Canadian Journal of Cardiology.
The new classification will allow for better risk stratification and more appropriate treatment and provide refined endpoints for clinical trials and translational research, according to the authors.
Dr Andreas Kumar
Currently, all patients with acute MI receive the same treatment, even though they may have different levels of tissue injury severity, statement author Andreas Kumar, MD, chair of the writing group and associate professor of medicine at Northern Ontario School of Medicine University in Sudbury, Ontario, Canada, told Medscape Medical News.
“In some cases, treatment for a mild stage 1 acute MI may be deadly for someone with stage 4 hemorrhagic MI,” said Kumar.
Technological Advances
The classification is based on decades of data. “The initial data were obtained with pathology studies in the 1970s. When cardiac MRI came around, around the year 2000, suddenly there was a noninvasive imaging method where we could investigate patients in vivo,” said Kumar. “We learned a lot about tissue changes in acute MI. And especially in the last 2 to 5 years, we have learned a lot about hemorrhagic MI. So, this then gave us enough knowledge to come up with this new classification.”
Rohan Dharmakumar, PhD
The idea of classifying acute MI came to Kumar and senior author Rohan Dharmakumar, PhD, executive director of the Krannert Cardiovascular Research Center at Indiana University School of Medicine, Indianapolis, when both were at the University of Toronto, Toronto, Ontario, Canada.
“This work has been years in the making,” Dharmakumar told Medscape. “We’ve been thinking about this for a long time, but we needed to get substantial layers of evidence to support the classification. We had a feeling about these stages for a long time, but that feeling needed to be substantiated.”
Last year, Dharmakumar and Kumar observed that damage to the heart from MI was not only a result of ischemia caused by a blocked artery, but also a result of bleeding in the myocardium after the artery had been opened. Their findings were published in the Journal of the American College of Cardiology.
The author of an accompanying editorial lauded the investigators “for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.”
“Hemorrhagic MI is a very dangerous injury because hemorrhage itself causes a lot of problems,” said Kumar. “We reported that there is infarct expansion after reperfusion, so once you open up the vessel, the heart attack actually gets larger. We also showed that the remodeling of these hearts is worse. These patients take a second hit with hemorrhage occurring in the myocardium.”
Classification and Staging
“The standard guideline therapy for somebody who comes into the hospital is to put in a stent, open the artery, have the patient stay in the hospital for 48 to 72 hours, and then be released home,” said Dharmukumar. “But here’s the problem. These two patients who are going back home have different levels of injury, yet they are taking the same medications. Even inside the hospital, we have heterogeneity in mortality risk. But we are not paying attention to one patient differently than the other, even though we should, because their injuries are very different.”
The CCS classification may provide endpoints and outcome measures beyond the commonly used clinical markers, which could lead to improved treatments to help patients recover from their cardiac events.
“We have this issue of rampant heart failure in acute MI survivors. We’ve gotten really good at saving patients from immediate death, but now we are just postponing some of the serious problems survivors are going to face,” said Dharmukumar. “What are we doing for these patients who are really at risk? We’ve been treating every single patient the same way and we have not been paying attention to the very different stages of injury.”
Dr Deepak L. Bhatt
In an accompanying editorial, Prakriti Gaba, MD, a clinical fellow in medicine at Brigham and Women’s Hospital in Boston, Massachusetts, and Deepak L. Bhatt, MD, MPH, director of the Mount Sinai Fuster Heart Hospital in New York, wrote, “There is no doubt that the classification system proposed by the investigators is important and timely, as acute MI continues to account for substantial morbidity and mortality worldwide.”
Imaging and staging could be useful in guiding appropriate therapy, Bhatt told Medscape. “The authors’ hope, which I think is a very laudable one, is that more finely characterizing exactly what the extent of damage is and what the mechanism of damage is in a heart attack will make it possible to develop therapies that are particularly targeted to each of the stages,” he said.
“It is quite common to have the ability to do cardiac MRI at experienced cardiovascular centers, although this may not be true for smaller community hospitals,” Bhatt added. “But at least at larger hospitals, this will allow for much finer evaluation and assessment of exactly what is going on in that particular patient and how extensive the heart muscle damage is. Eventually, this will facilitate the development of therapies that are specifically targeted to treat each stage.”
Kumar is partly supported by a research grant from the Northern Ontario Academic Medicine Association. Dharmakumar was funded in part by grants from the US National Institutes of Health. Dharmakumar has an ownership interest in Cardio-Theranostics. Bhatt has served on a dvisory boards for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys. He is a member of the board of directors of or holds stock in Angiowave, Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft. He has worked as a consultant for Broadview Ventures, and Hims. He has received honoraria from the American College of Cardiology, Arnold and Porter law firm, Baim Institute for Clinical Research, Belvoir Publications, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, WebMD, and Wiley. Full disclosures are available online.
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